ArticleGenes & development2013
Cisplatin causes cell death via TAB1 regulation of p53/MDM2/MDMX circuitry.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 40 citations in OpenAlex.
- Targeting the MDM2-MDM4 interaction interface reveals an otherwise therapeutically active wild-type p53 in colorectal cancer.Molecular oncology · 2025Article
- PP2C phosphatases-terminators of suicidal thoughts.Cell death & disease · 2024Review
- Nutlin-3 suppresses tumorigenesis and progression of oral squamous cell carcinoma and enhances chemosensitivity to cisplatin.Cytotechnology · 2023Article
- Pseudophosphatases as Regulators of MAPK Signaling.International journal of molecular sciences · 2021Review
- Article
- Shift in MSL1 alternative polyadenylation in response to DNA damage protects cancer cells from chemotherapeutic agent-induced apoptosis.Cell reports · 2021Article
- The Roles of Pseudophosphatases in Disease.International journal of molecular sciences · 2021Review
- Inhibition of the mTOR pathway and reprogramming of protein synthesis by MDM4 reduce ovarian cancer metastatic properties.Cell death & disease · 2021Article
- FZR1 as a novel biomarker for breast cancer neoadjuvant chemotherapy prediction.Cell death & disease · 2020Article
- Recombinant Dual-target MDM2/MDMX Inhibitor Reverses Doxorubicin Resistance through Activation of the TAB1/TAK1/p38 MAPK Pathway in Wild-type p53 Multidrug-resistant Breast Cancer Cells.Journal of Cancer · 2020Article
- Targeting MDMX for Cancer Therapy: Rationale, Strategies, and Challenges.Frontiers in oncology · 2020Review
- TheFrontiers in oncology · 2020Article
- Estrogens Counteract Platinum-Chemosensitivity by Modifying the Subcellular Localization of MDM4.Cancers · 2019Article
- Dual-target MDM2/MDMX inhibitor increases the sensitization of doxorubicin and inhibits migration and invasion abilities of triple-negative breast cancer cells through activation of TAB1/TAK1/p38 MAPK pathway.Cancer biology & therapy · 2019Article
- p53 sensitizes chemoresistant non-small cell lung cancer via elevation of reactive oxygen species and suppression of EGFR/PI3K/AKT signaling.Cancer cell international · 2019Article
- Tailoring Chemotherapy for the African-Centric S47 Variant of TP53.Cancer research · 2018Article
- p53-independent Noxa induction by cisplatin is regulated by ATF3/ATF4 in head and neck squamous cell carcinoma cells.Molecular oncology · 2018Article
- Compound mutations in Bmpr1a and Tak1 synergize facial deformities via increased cell death.Genesis (New York, N.Y. : 2000) · 2018Article
- MDM4 actively restrains cytoplasmic mTORC1 by sensing nutrient availability.Molecular cancer · 2017Article
- Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The interdependence of p53 and MDM2 is critical for proper cell survival and cell death and, when altered, can lead to tumorigenesis. Mitogen-activated protein kinase (MAPK) signaling pathways function in a wide variety of cellular processes, including cell growth, migration, differentiation, and death. Here we discovered that transforming growth factor β-activated kinase 1 (TAK1)-binding protein 1 (TAB1), an activator of TAK1 and of p38α, associates with and inhibits the E3 ligase activity of MDM2 toward p53 and its homolog, MDMX. Depletion of TAB1 inhibits MDM2 siRNA-mediated p53 accumulation and p21 induction, partially rescuing cell cycle arrest induced by MDM2 ablation. Interestingly, of several agents commonly used as DNA-damaging therapeutics, only cell death caused by cisplatin is mitigated by knockdown of TAB1. Two mechanisms are required for TAB1 to regulate apoptosis in cisplatin-treated cells. First, p38α is activated by TAB1 to phosphorylate p53 N-terminal sites, leading to selective induction of p53 targets such as NOXA. Second, MDMX is stabilized in a TAB1-dependent manner and is required for cell death after cisplatin treatment. Interestingly TAB1 levels are relatively low in cisplatin-resistant clones of ovarian cells and in ovarian patient's tumors compared with normal ovarian tissue. Together, our results indicate that TAB1 is a potential tumor suppressor that serves as a functional link between p53-MDM2 circuitry and a key MAPK signaling pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.